VP-1-16 undergoes O-demethylation to generate active intermediates that binds to protein and DNA. The O-demethylation is P450 dependant. Peroxidases, such as horseradish or prostaglandin synthetase, also activate VP-16 and VM-26 to their O- Quinonederivatives, and catalyze binding of reactive intermediates of DNA. Enzymatic activation to reactive intermediates may be important in the biological activities of VP-16 and VM-26.